PROJECT SUMMARY/ABSTRACT Between 3% and 9% of the general population have a voice problem at any given point in time. Such problems have serious psychological, functional and economic consequences, in particular for teachers and professional voice users. The most severe conditions affecting voice are when vocal fold mucosa is lost or replaced by scar. For large mucosa voids or scarring, we propose to deliver effective biomaterials into the vocal fold site using an endoscopy-fit handheld bioprinter. This approach may help regenerate a functional vocal fold tissue and restore voice production. Biomimetic self-healing hydrogels act like fluid flow during needle extrusion and rapidly solidify when the precursors mix, thus allowing in situ deposition of vocal fold implants via extrusion. We will optimize a self-healing hydrogel formulation that adheres and seals quickly to the host tissue, in which phenol-based components will be used as adhesives due to their biocompatibility and tunable adhesion strength. We will assess the biocompatibility of the proposed hydrogel using human vocal fold fibroblasts. The hydrogel will feed a custom-made handheld bioprinter with tunable length and coaxial geometry. We will explore bioprinting strategies to deposit such vocal fold implants via changing design parameters in the handheld bioprinter and extrusion of the proposed hydrogel to vocal fold sites. We will test our handheld bioprinter using ex vivo larynges, and will optimize the deposition parameters. In the last step, we will incorporate an animal model for in vivo assessment of our hydrogel and to justify the clinical efficiency of our proposed handheld bioprinter. Our overarching goal is to translate the proposed self-healing hydrogel system and the bioprinting platform into otolaryngology clinics in the United States when we successfully complete this grant.